ID VPS4B_HUMAN Reviewed; 444 AA. AC O75351; Q69HW4; Q9GZS7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 16-JAN-2004, sequence version 2. DT 27-MAR-2024, entry version 208. DE RecName: Full=Vacuolar protein sorting-associated protein 4B {ECO:0000305}; DE EC=3.6.4.6 {ECO:0000269|PubMed:18687924}; DE AltName: Full=Cell migration-inducing gene 1 protein; DE AltName: Full=Suppressor of K(+) transport growth defect 1; DE Short=Protein SKD1; GN Name=VPS4B {ECO:0000312|HGNC:HGNC:10895}; Synonyms=SKD1, VPS42; GN ORFNames=MIG1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH VPS4A, SUBCELLULAR RP LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF GLU-235. RX PubMed=11563910; DOI=10.1006/jmbi.2001.4917; RA Scheuring S., Roehricht R.A., Schoening-Burkhardt B., Beyer A., Mueller S., RA Abts H.F., Koehrer K.; RT "Mammalian cells express two VPS4 proteins both of which are involved in RT intracellular protein trafficking."; RL J. Mol. Biol. 312:469-480(2001). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Skin; RX PubMed=12594041; DOI=10.1016/s0378-1119(02)01205-2; RA Beyer A., Scheuring S., Mueller S., Mincheva A., Lichter P., Koehrer K.; RT "Comparative sequence and expression analyses of four mammalian VPS4 RT genes."; RL Gene 305:47-59(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175; RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., RA Wang Y.-X., Chen S.-J., Chen Z.; RT "Identification of genes expressed in human CD34(+) hematopoietic RT stem/progenitor cells by expressed sequence tags and efficient full-length RT cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kim J.W.; RT "Identification of a human cell migration gene 1."; RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH CHMP2A. RX PubMed=11559748; DOI=10.1242/jcs.114.13.2395; RA Howard T.L., Stauffer D.R., Degnin C.R., Hollenberg S.M.; RT "CHMP1 functions as a member of a newly defined family of vesicle RT trafficking proteins."; RL J. Cell Sci. 114:2395-2404(2001). RN [8] RP FUNCTION IN HIV-1 BUDDING (MICROBIAL INFECTION), INTERACTION WITH CHMP1A; RP CHMP1B CHMP2A; CHMP4B AND CHMP6, AND SUBCELLULAR LOCATION. RX PubMed=14505570; DOI=10.1016/s0092-8674(03)00714-1; RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y., RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A., RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.; RT "The protein network of HIV budding."; RL Cell 114:701-713(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [11] RP MUTAGENESIS OF ALA-15 AND LEU-66, AND FUNCTION (MICROBIAL INFECTION). RX PubMed=18606141; DOI=10.1016/j.devcel.2008.05.014; RA Kieffer C., Skalicky J.J., Morita E., De Domenico I., Ward D.M., Kaplan J., RA Sundquist W.I.; RT "Two distinct modes of ESCRT-III recognition are required for VPS4 RT functions in lysosomal protein targeting and HIV-1 budding."; RL Dev. Cell 15:62-73(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [13] RP INTERACTION WITH VTA1, AND MUTAGENESIS OF 390-GLY--TRP-396. RX PubMed=18385515; DOI=10.1091/mbc.e07-12-1263; RA Shim S., Merrill S.A., Hanson P.I.; RT "Novel interactions of ESCRT-III with LIP5 and VPS4 and their implications RT for ESCRT-III disassembly."; RL Mol. Biol. Cell 19:2661-2672(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [16] RP FUNCTION, ASSOCIATION WITH THE CHMP2A-CHMP3 POLYMER, ELECTRON MICROSCOPY, RP AND CATALYTIC ACTIVITY. RX PubMed=18687924; DOI=10.1126/science.1161070; RA Lata S., Schoehn G., Jain A., Pires R., Piehler J., Goettlinger H.G., RA Weissenhorn W.; RT "Helical structures of ESCRT-III are disassembled by VPS4."; RL Science 321:1354-1357(2008). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP INTERACTION WITH IST1. RX PubMed=19129479; DOI=10.1091/mbc.e08-05-0475; RA Bajorek M., Morita E., Skalicky J.J., Morham S.G., Babst M., RA Sundquist W.I.; RT "Biochemical analyses of human IST1 and its function in cytokinesis."; RL Mol. Biol. Cell 20:1360-1373(2009). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-102 AND SER-108, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP FUNCTION. RX PubMed=22660413; DOI=10.1038/ncb2502; RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A., RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P., RA David G.; RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes."; RL Nat. Cell Biol. 14:677-685(2012). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-93; SER-102; SER-108 AND RP SER-410, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP STRUCTURE BY NMR OF 1-77, DOMAIN, AND VARIANT MET-58. RX PubMed=16018968; DOI=10.1016/j.bbrc.2005.06.110; RA Takasu H., Jee J.G., Ohno A., Goda N., Fujiwara K., Tochio H., RA Shirakawa M., Hiroaki H.; RT "Structural characterization of the MIT domain from human Vps4b."; RL Biochem. Biophys. Res. Commun. 334:460-465(2005). RN [27] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 123-444, SUBUNIT, INTERACTION WITH RP VTA1, MUTAGENESIS OF 208-TRP-LEU-209 AND GLY-210, AND FUNCTION (MICROBIAL RP INFECTION). RX PubMed=16193069; DOI=10.1038/sj.emboj.7600818; RA Scott A., Chung H.Y., Gonciarz-Swiatek M., Hill G.C., Whitby F.G., RA Gaspar J., Holton J.M., Viswanathan R., Ghaffarian S., Hill C.P., RA Sundquist W.I.; RT "Structural and mechanistic studies of VPS4 proteins."; RL EMBO J. 24:3658-3669(2005). RN [28] RP STRUCTURE BY NMR OF 1-108. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of MIT domain from human SKD1."; RL Submitted (NOV-2005) to the PDB data bank. RN [29] RP STRUCTURE BY NMR OF 1-86 IN COMPLEX WITH CHMP2B, AND INTERACTION WITH RP CHMP1B. RX PubMed=17928862; DOI=10.1038/nature06172; RA Stuchell-Brereton M.D., Skalicky J.J., Kieffer C., Karren M.A., RA Ghaffarian S., Sundquist W.I.; RT "ESCRT-III recognition by VPS4 ATPases."; RL Nature 449:740-744(2007). CC -!- FUNCTION: Involved in late steps of the endosomal multivesicular bodies CC (MVB) pathway. Recognizes membrane-associated ESCRT-III assemblies and CC catalyzes their ATP-dependent disassembly, possibly in combination with CC membrane fission (PubMed:18687924). Redistributes the ESCRT-III CC components to the cytoplasm for further rounds of MVB sorting. MVBs CC contain intraluminal vesicles (ILVs) that are generated by invagination CC and scission from the limiting membrane of the endosome and mostly are CC delivered to lysosomes enabling degradation of membrane proteins, such CC as stimulated growth factor receptors, lysosomal enzymes and lipids. CC VPS4A/B are required for the exosomal release of SDCBP, CD63 and CC syndecan (PubMed:22660413). {ECO:0000269|PubMed:11563910, CC ECO:0000269|PubMed:18687924, ECO:0000269|PubMed:22660413}. CC -!- FUNCTION: (Microbial infection) In conjunction with the ESCRT machinery CC also appears to function in topologically equivalent membrane fission CC events, such as the terminal stages of cytokinesis and enveloped virus CC budding (HIV-1 and other lentiviruses). {ECO:0000269|PubMed:14505570, CC ECO:0000269|PubMed:16193069, ECO:0000269|PubMed:18606141}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.6; CC Evidence={ECO:0000269|PubMed:18687924}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13066; CC Evidence={ECO:0000305|PubMed:18687924}; CC -!- SUBUNIT: Proposed to be monomeric or homodimeric in nucleotide-free CC form and to oligomerize upon binding to ATP to form two stacked CC hexameric or heptameric rings with a central pore through which ESCRT- CC III substrates are translocated in an ATP-dependent manner. In vitro, CC associates on the inside of a helical tubular structure formed by a CC CHMP2A-CHMP3 polymer. Interacts with CHMP1A, CHMP1B, CHMP2A, CHMP4B and CC CHMP6. Interacts with VPS4A; the interaction suggests a heteromeric CC assembly with VPS4A. Interacts with VTA1. {ECO:0000269|PubMed:11559748, CC ECO:0000269|PubMed:11563910, ECO:0000269|PubMed:14505570, CC ECO:0000269|PubMed:16193069, ECO:0000269|PubMed:17928862, CC ECO:0000269|PubMed:18385515, ECO:0000269|PubMed:19129479}. CC -!- INTERACTION: CC O75351; P54253: ATXN1; NbExp=3; IntAct=EBI-2514459, EBI-930964; CC O75351; Q9HD42: CHMP1A; NbExp=3; IntAct=EBI-2514459, EBI-1057156; CC O75351; Q9UQN3-1: CHMP2B; NbExp=2; IntAct=EBI-2514459, EBI-15663586; CC O75351; Q9NZZ3: CHMP5; NbExp=6; IntAct=EBI-2514459, EBI-751303; CC O75351; P42858: HTT; NbExp=3; IntAct=EBI-2514459, EBI-466029; CC O75351; Q9BW62: KATNAL1; NbExp=3; IntAct=EBI-2514459, EBI-743591; CC O75351; Q96K21: ZFYVE19; NbExp=7; IntAct=EBI-2514459, EBI-6448240; CC O75351; Q96K21-3: ZFYVE19; NbExp=3; IntAct=EBI-2514459, EBI-10187928; CC -!- SUBCELLULAR LOCATION: Late endosome membrane CC {ECO:0000250|UniProtKB:P46467}; Peripheral membrane protein CC {ECO:0000305}. Note=Membrane-associated in the prevacuolar endosomal CC compartment. Localized in HIV-1 particles purified from acutely CC infected cells. {ECO:0000269|PubMed:14505570}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:11563910}. CC -!- DOMAIN: The MIT domain serves as an adapter for ESCRT-III proteins. It CC forms an asymmetric three-helix bundle that binds amphipathic MIM (MIT CC interacting motif) helices along the groove between MIT helices 2 and 3 CC present in a subset of ESCRT-III proteins thus establishing the CC canonical MIM-MIT interaction. In an extended conformation along the CC groove between helices 1 and 3, also binds to a type-2 MIT interacting CC motif (MIM2). {ECO:0000269|PubMed:16018968}. CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF195514; AAG33022.1; -; mRNA. DR EMBL; AF282904; AAG01471.1; -; Genomic_DNA. DR EMBL; AF038960; AAC39874.1; -; mRNA. DR EMBL; AY232629; AAP59551.1; -; mRNA. DR EMBL; CH471096; EAW63143.1; -; Genomic_DNA. DR EMBL; BC039574; AAH39574.1; -; mRNA. DR CCDS; CCDS11983.1; -. DR RefSeq; NP_004860.2; NM_004869.3. DR PDB; 1WR0; NMR; -; A=1-77. DR PDB; 1XWI; X-ray; 2.80 A; A=123-444. DR PDB; 2CPT; NMR; -; A=1-104. DR PDB; 2JQH; NMR; -; A=1-86. DR PDB; 2JQK; NMR; -; A=1-86. DR PDB; 4U7Y; X-ray; 2.50 A; A=1-89. DR PDB; 7L9X; X-ray; 2.81 A; A=1-444. DR PDBsum; 1WR0; -. DR PDBsum; 1XWI; -. DR PDBsum; 2CPT; -. DR PDBsum; 2JQH; -. DR PDBsum; 2JQK; -. DR PDBsum; 4U7Y; -. DR PDBsum; 7L9X; -. DR AlphaFoldDB; O75351; -. DR SMR; O75351; -. DR BioGRID; 114901; 89. DR ComplexPortal; CPX-338; VPS4A/B complex. DR DIP; DIP-53790N; -. DR IntAct; O75351; 22. DR MINT; O75351; -. DR STRING; 9606.ENSP00000238497; -. DR BindingDB; O75351; -. DR ChEMBL; CHEMBL2311229; -. DR GlyGen; O75351; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O75351; -. DR MetOSite; O75351; -. DR PhosphoSitePlus; O75351; -. DR BioMuta; VPS4B; -. DR EPD; O75351; -. DR jPOST; O75351; -. DR MassIVE; O75351; -. DR MaxQB; O75351; -. DR PaxDb; 9606-ENSP00000238497; -. DR PeptideAtlas; O75351; -. DR ProteomicsDB; 49918; -. DR Pumba; O75351; -. DR Antibodypedia; 23094; 224 antibodies from 31 providers. DR DNASU; 9525; -. DR Ensembl; ENST00000238497.10; ENSP00000238497.4; ENSG00000119541.10. DR GeneID; 9525; -. DR KEGG; hsa:9525; -. DR MANE-Select; ENST00000238497.10; ENSP00000238497.4; NM_004869.4; NP_004860.2. DR UCSC; uc002lix.4; human. DR AGR; HGNC:10895; -. DR CTD; 9525; -. DR DisGeNET; 9525; -. DR GeneCards; VPS4B; -. DR HGNC; HGNC:10895; VPS4B. DR HPA; ENSG00000119541; Low tissue specificity. DR MalaCards; VPS4B; -. DR MIM; 609983; gene. DR neXtProt; NX_O75351; -. DR OpenTargets; ENSG00000119541; -. DR Orphanet; 99789; Dentin dysplasia type I. DR PharmGKB; PA35795; -. DR VEuPathDB; HostDB:ENSG00000119541; -. DR eggNOG; KOG0739; Eukaryota. DR GeneTree; ENSGT00940000154973; -. DR HOGENOM; CLU_000688_21_2_1; -. DR InParanoid; O75351; -. DR OMA; AEEMTWM; -. DR OrthoDB; 276256at2759; -. DR PhylomeDB; O75351; -. DR TreeFam; TF105012; -. DR PathwayCommons; O75351; -. DR Reactome; R-HSA-162588; Budding and maturation of HIV virion. DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT). DR SignaLink; O75351; -. DR BioGRID-ORCS; 9525; 68 hits in 1162 CRISPR screens. DR ChiTaRS; VPS4B; human. DR EvolutionaryTrace; O75351; -. DR GeneWiki; VPS4B; -. DR GenomeRNAi; 9525; -. DR Pharos; O75351; Tchem. DR PRO; PR:O75351; -. DR Proteomes; UP000005640; Chromosome 18. DR RNAct; O75351; Protein. DR Bgee; ENSG00000119541; Expressed in esophagus squamous epithelium and 202 other cell types or tissues. DR ExpressionAtlas; O75351; baseline and differential. DR GO; GO:1904949; C:ATPase complex; NAS:ComplexPortal. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005768; C:endosome; IDA:MGI. DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0090543; C:Flemming body; IDA:UniProtKB. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0030496; C:midbody; NAS:ComplexPortal. DR GO; GO:0005643; C:nuclear pore; NAS:ComplexPortal. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; NAS:ComplexPortal. DR GO; GO:0000922; C:spindle pole; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl. DR GO; GO:0097352; P:autophagosome maturation; NAS:ComplexPortal. DR GO; GO:0006914; P:autophagy; NAS:ComplexPortal. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0030301; P:cholesterol transport; IEA:Ensembl. DR GO; GO:0016197; P:endosomal transport; IDA:MGI. DR GO; GO:0032510; P:endosome to lysosome transport via multivesicular body sorting pathway; IMP:UniProtKB. DR GO; GO:1904903; P:ESCRT III complex disassembly; IDA:UniProtKB. DR GO; GO:0060856; P:establishment of blood-brain barrier; IEA:Ensembl. DR GO; GO:0061738; P:late endosomal microautophagy; IEA:Ensembl. DR GO; GO:0061764; P:late endosome to lysosome transport via multivesicular body sorting pathway; NAS:ComplexPortal. DR GO; GO:0016236; P:macroautophagy; NAS:ParkinsonsUK-UCL. DR GO; GO:0090148; P:membrane fission; NAS:ComplexPortal. DR GO; GO:0061952; P:midbody abscission; IMP:UniProtKB. DR GO; GO:0007080; P:mitotic metaphase chromosome alignment; IMP:UniProtKB. DR GO; GO:0036258; P:multivesicular body assembly; NAS:ParkinsonsUK-UCL. DR GO; GO:0071985; P:multivesicular body sorting pathway; NAS:ComplexPortal. DR GO; GO:1903542; P:negative regulation of exosomal secretion; IMP:UniProtKB. DR GO; GO:0031468; P:nuclear membrane reassembly; NAS:ComplexPortal. DR GO; GO:0006997; P:nucleus organization; IMP:UniProtKB. DR GO; GO:0001778; P:plasma membrane repair; NAS:ComplexPortal. DR GO; GO:1903724; P:positive regulation of centriole elongation; IMP:UniProtKB. DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0006813; P:potassium ion transport; IEA:Ensembl. DR GO; GO:0051261; P:protein depolymerization; IDA:UniProtKB. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0010824; P:regulation of centrosome duplication; IMP:UniProtKB. DR GO; GO:1901673; P:regulation of mitotic spindle assembly; IMP:UniProtKB. DR GO; GO:0033993; P:response to lipid; IDA:UniProtKB. DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB. DR GO; GO:0090611; P:ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway; IMP:UniProtKB. DR GO; GO:0007033; P:vacuole organization; IBA:GO_Central. DR GO; GO:0046761; P:viral budding from plasma membrane; IMP:UniProtKB. DR GO; GO:0039702; P:viral budding via host ESCRT complex; IGI:UniProtKB. DR CDD; cd02678; MIT_VPS4; 1. DR CDD; cd19521; RecA-like_VPS4; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.20.58.80; Phosphotransferase system, lactose/cellobiose-type IIA subunit; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR041569; AAA_lid_3. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR003960; ATPase_AAA_CS. DR InterPro; IPR007330; MIT_dom. DR InterPro; IPR036181; MIT_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR015415; Spast_Vps4_C. DR InterPro; IPR045253; VPS4_MIT. DR PANTHER; PTHR23074; AAA DOMAIN-CONTAINING; 1. DR PANTHER; PTHR23074:SF72; VACUOLAR PROTEIN SORTING-ASSOCIATED PROTEIN 4B; 1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF17862; AAA_lid_3; 1. DR Pfam; PF04212; MIT; 1. DR Pfam; PF09336; Vps4_C; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM00745; MIT; 1. DR SUPFAM; SSF116846; MIT domain; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00674; AAA; 1. DR Genevisible; O75351; HS. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cell division; Coiled coil; KW Endosome; Hydrolase; Membrane; Nucleotide-binding; Phosphoprotein; KW Protein transport; Reference proteome; Transport. FT CHAIN 1..444 FT /note="Vacuolar protein sorting-associated protein 4B" FT /id="PRO_0000084767" FT DOMAIN 4..82 FT /note="MIT" FT REGION 77..117 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 19..82 FT /evidence="ECO:0000255" FT COMPBIAS 77..116 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 174..181 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255" FT MOD_RES 93 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 102 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18088087, ECO:0007744|PubMed:18318008, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 108 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:24275569" FT MOD_RES 410 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VARIANT 58 FT /note="I -> M (induces thermal instability; FT dbSNP:rs17688948)" FT /evidence="ECO:0000269|PubMed:16018968" FT /id="VAR_023385" FT MUTAGEN 15 FT /note="A->D: Reduces HIV-1 release 10-fold; when associated FT with D-66." FT /evidence="ECO:0000269|PubMed:18606141" FT MUTAGEN 15 FT /note="A->D: Reduces HIV-1 release 2-fold." FT /evidence="ECO:0000269|PubMed:18606141" FT MUTAGEN 66 FT /note="L->D: Reduces HIV-1 release 10-fold; when associated FT with D-15." FT /evidence="ECO:0000269|PubMed:18606141" FT MUTAGEN 66 FT /note="L->D: Reduces HIV-1 release 3-fold." FT /evidence="ECO:0000269|PubMed:18606141" FT MUTAGEN 208..209 FT /note="WL->AA: Strongly impairs HIV-1 release." FT /evidence="ECO:0000269|PubMed:16193069" FT MUTAGEN 210 FT /note="G->A: Impairs HIV-1 release." FT /evidence="ECO:0000269|PubMed:16193069" FT MUTAGEN 235 FT /note="E->Q: Defective in vacuolar protein sorting." FT /evidence="ECO:0000269|PubMed:11563910" FT MUTAGEN 390..396 FT /note="Missing: Abolishes interaction with VTA1." FT /evidence="ECO:0000269|PubMed:18385515" FT CONFLICT 114 FT /note="K -> R (in Ref. 3; AAC39874)" FT /evidence="ECO:0000305" FT CONFLICT 127 FT /note="E -> D (in Ref. 3; AAC39874)" FT /evidence="ECO:0000305" FT CONFLICT 342 FT /note="S -> G (in Ref. 3; AAC39874)" FT /evidence="ECO:0000305" FT TURN 1..3 FT /evidence="ECO:0007829|PDB:1WR0" FT HELIX 6..24 FT /evidence="ECO:0007829|PDB:4U7Y" FT HELIX 27..47 FT /evidence="ECO:0007829|PDB:4U7Y" FT HELIX 52..81 FT /evidence="ECO:0007829|PDB:4U7Y" FT STRAND 87..89 FT /evidence="ECO:0007829|PDB:2CPT" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 140..155 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 157..159 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 168..178 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 180..190 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 195..200 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 213..225 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 227..234 FT /evidence="ECO:0007829|PDB:1XWI" FT TURN 235..237 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 238..240 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 243..245 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 250..263 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 272..279 FT /evidence="ECO:0007829|PDB:1XWI" FT TURN 281..283 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 286..290 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 294..297 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 303..314 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 323..331 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 338..349 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 351..358 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 360..368 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 375..383 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 386..388 FT /evidence="ECO:0007829|PDB:1XWI" FT STRAND 391..393 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 396..398 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 401..403 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 411..419 FT /evidence="ECO:0007829|PDB:1XWI" FT HELIX 427..438 FT /evidence="ECO:0007829|PDB:1XWI" FT TURN 440..443 FT /evidence="ECO:0007829|PDB:7L9X" SQ SEQUENCE 444 AA; 49302 MW; 9D565E4B20AF73FB CRC64; MSSTSPNLQK AIDLASKAAQ EDKAGNYEEA LQLYQHAVQY FLHVVKYEAQ GDKAKQSIRA KCTEYLDRAE KLKEYLKNKE KKAQKPVKEG QPSPADEKGN DSDGEGESDD PEKKKLQNQL QGAIVIERPN VKWSDVAGLE GAKEALKEAV ILPIKFPHLF TGKRTPWRGI LLFGPPGTGK SYLAKAVATE ANNSTFFSIS SSDLVSKWLG ESEKLVKNLF QLARENKPSI IFIDEIDSLC GSRSENESEA ARRIKTEFLV QMQGVGVDND GILVLGATNI PWVLDSAIRR RFEKRIYIPL PEPHARAAMF KLHLGTTQNS LTEADFRELG RKTDGYSGAD ISIIVRDALM QPVRKVQSAT HFKKVRGPSR ADPNHLVDDL LTPCSPGDPG AIEMTWMDVP GDKLLEPVVS MSDMLRSLSN TKPTVNEHDL LKLKKFTEDF GQEG //